Cell Cycle includes many processes necessary for successful self-replication, and consists of DNA synthesis (S) and mitosis (M) phases separated by gap phases in the order G1–S–G2–M. S phase and M phase are usually separated by gap phases called G1 and G2, when cell-cycle progression can be regulated by various intracellular and extracellular signals. In order to move from one phase of its life cycle to the next, a cell must pass through numerous checkpoints. At each checkpoint, specialized proteins determine whether the necessary conditions exist. Progression through G1 phase is controlled by pRB proteins, and phosphorylation of pRB proteins by CDKs releases E2F factors, promoting the transition to S phase. The G2/M transition that commits cells to division is a default consequence of initiating the cell cycle at the G1/S transition, many proteins, such Wee1, PLK1 and cdc25, is involved the regulation of this process. The best-understood checkpoints are those activated by DNA damage and problems with DNA replication.

DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Genome instability arises if cells initiate mitosis when chromosomes are only partially replicated or are damaged by a double-strand DNA break (DSB). To prevent cells with damaged DNA from entering mitosis, ATR inhibits cyclin B/Cdk1 activation by stimulating the Cdk1 inhibitory kinase Wee1 and inhibiting Cdc25C via Chk1, besides, ATM and ATR also initiate DNA repair by phosphorylating several other substrates.

In cancer cells, the cell cycle regulators as well as other elements of the DDR pathway have been found to protect tumor cells from different stresses and to promote tumor progression. Thus, cell cycle proteins that directly regulate cell cycle progression (such as CDKs), as well as checkpoint kinases, Aurora kinases and PLKs, are promising targets in cancer therapy.

References:
[1] Rhind N, et al. Cold Spring Harb Perspect Biol. 2012 Oct; 4(10): a005942.
[2] Duronio RJ, et al. Cold Spring Harb Perspect Biol. 2013 Mar; 5(3): a008904.
[3] Liu W, et al. Mol Cancer. 2017 Mar 14;16(1):60.
[4] Ghelli Luserna di Rora' A, et al. J Hematol Oncol. 2017 Mar 29;10(1):77.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
Autophagy LRRK2 ULK Mitophagy
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
Cytoskeleton >
Arp2/3 Complex Dynamin Gap Junction Protein Integrin Kinesin Microtubule/Tubulin Mps1 Myosin PAK
Epigenetics >
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
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Metabolic Enzyme/Protease >
15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
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Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
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Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
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Vitamin D Related >
VD/VDR
Others >
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Topotecan hydrochloride

Topotecan Hydrochloride (SKF 104864A; NSC 609669) is a Topoisomerase I inhibitor with potent antineoplastic activities.

  • CAS Number: 119413-54-6
  • MF: C23H24ClN3O5
  • MW: 421.446
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 782.9±60.0 °C at 760 mmHg
  • Melting Point: 213-218ºC
  • Flash Point: 427.3±32.9 °C

2'-Deoxyadenosine-5'-triphosphate-d14 dilithium

2'-Deoxyadenosine-5'-triphosphate-d14 (dATP-d14) dilithium is deuterium labeled 2'-Deoxyadenosine-5'-triphosphate (HY-136648). 2'-Deoxyadenosine-5'-triphosphate (dATP) is a nucleotide used in cells for DNA synthesis (or replication), as a substrate of DNA polymerase.

  • CAS Number: 2687960-68-3
  • MF: C10D14Li2N5O12P3
  • MW: 517.13
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LMP744 hydrochloride

LMP744 hydrochloride (MJ-III65 hydrochloride) is a DNA intercalator and Topoisomerase (Top1) inhibitor with antitumor activity[1].

  • CAS Number: 308246-57-3
  • MF: C24H25ClN2O7
  • MW: 488.91800
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5'-O-(Dimethoxytrityl)-N-isobutyryl-2'-deoxycytidine

5'-O-DMT-ibu-dC can be used in the synthesis of oligodeoxyribonucleotides[1].

  • CAS Number: 100898-62-2
  • MF: C34H37N3O7
  • MW: 599.67300
  • Catalog: DNA/RNA Synthesis
  • Density: 1.25±0.1 g/cm3(Predicted)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TBBz

4,5,6,7-Tetrabromobenzimidazole is a selective and ATP competitive CK2 (casein kinase 2) inhibitor[1].

  • CAS Number: 577779-57-8
  • MF: C7H2Br4N2
  • MW: 433.72000
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 330-332ºC
  • Flash Point: N/A

NU1025

NU1025 is a potent PARP inhibitor with an IC50 of 400 nM and a Ki of 48 nM. NU1025 potentiates the cytotoxicity of ionizing radiation and anticancer drugs. NU1025 has anti-cancer and neuroprotective activity[1][2][3].

  • CAS Number: 90417-38-2
  • MF: C9H8N2O2
  • MW: 176.172
  • Catalog: PARP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 345.4±44.0 °C at 760 mmHg
  • Melting Point: 253-258ºC
  • Flash Point: 162.7±28.4 °C

Hydroxyurea

Hydroxyurea is a cell apoptosis inducer that inhibitDNA synthesis through inhibition of ribonucleotide reductase.

  • CAS Number: 127-07-1
  • MF: CH4N2O2
  • MW: 76.055
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 222.1±23.0 °C at 760 mmHg
  • Melting Point: 135-140 °C
  • Flash Point: 88.1±22.6 °C

2-Chloro-6-(furan-2-yl) purine-beta-D-(3’-deoxy-3’-fluoro)-riboside

2-Chloro-6-(furan-2-yl) purine-beta-D-(3’-deoxy-3’-fluoro)-riboside is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 1612192-00-3
  • MF: C14H12ClFN4O4
  • MW: 354.72
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 556.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 290.3±32.9 °C

PD 0332991-d8

Palbociclib D8 (PD 0332991 D8) is a deuterium labeled Palbociclib. Palbociclib is a selective and orally active CDK4 and CDK6 inhibitor with IC50s of 11 and 16 nM, respectively. Palbociclib has no activity against other protein kinases. Palbociclib has potently anticancer activities[1].

  • CAS Number: 1628752-83-9
  • MF: C24H21D8N7O2
  • MW: 455.58
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chlamydocin

Chlamydocin, a fungal metabolite, is a highly potent HDAC inhibitor, with an IC50 of 1.3 nM. Chlamydocin exhibits potent antiproliferative and anticancer activities. Chlamydocin induces apoptosis by activating caspase-3[1].

  • CAS Number: 53342-16-8
  • MF: C28H38N4O6
  • MW: 526.62500
  • Catalog: Apoptosis
  • Density: 1.27g/cm3
  • Boiling Point: 861.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 475ºC

5-(N-Isopentenyl-N-trifluoroacetyl) aminomethyluridine

5-(N-Isopentenyl-N-trifluoroacetyl) aminomethyluridine is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 1613530-43-0
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRCA1-IN-2

BRCA1-IN-2 (compound 15) is a cell-permeable protein-protein interaction (PPI) inhibitor for BRCA1 with an IC50 of 0.31 μM and a Kd of 0.3 μM, which shows antitumor activities via the disruption of BRCA1 (BRCT)2/protein interactions[1].

  • CAS Number: 1622262-55-8
  • MF: C26H33N4O7P
  • MW: 544.54
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dehydroaltenusin

Dehydroaltenusin is a small molecule selective inhibitor of eukaryotic DNA polymerase α, a type of antibiotic produced by a fungus with an IC50 value of 0.68 μM. The inhibitory mode of action of dehydroaltenusin against mammalian pol α activity is competitive with respect to the DNA template primer (Ki=0.23 µM) and non-competitive with respect to the 2'-deoxyribonucleoside 5'-triphosphate substrate (Ki=0.18 µM)[1].Dehydroaltenusin arrests the cancer cell cycle at the S-phase and triggers apoptosis[1].Dehydroaltenusin possesses anti-tumor activity against human adenocarcinoma tumor in vivo[1].

  • CAS Number: 31186-13-7
  • MF: C15H12O6
  • MW: 288.25
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Allyl-7,8-dihydro-8-oxo-9-(β-D-xylofuranosyl) guanine

7-Allyl-7,8-dihydro-8-oxo-9-(β-D-xylofuranosyl) guanine is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 2389988-25-2
  • MF: C13H17N5O6
  • MW: 339.30
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PBOX 6

PBOX 6 is a pyrrolo-1,5-benzoxazepine (PBOX) compound, acts as a microtubule-depolymerizing agent and an apoptotic agent.

  • CAS Number: 290814-68-5
  • MF: C25H20N2O3
  • MW: 396.438
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 580.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.0±30.1 °C

5’-O-DMTr-3’-deoxyuridine 2’-CED phosphoramidite

5’-O-DMTr-3’-deoxyuridine 2’-CED phosphoramidite is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 161503-98-6
  • MF: C39H47N4O8P
  • MW: 730.79
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tetrapeptide

Tetrapeptide, an analogue of α-MSH, induces melanin synthesis. Tetrapeptide diminishes DNA damage by reducing the production of reactive oxidative species and enhancing repair of DNA photoproducts[1].

  • CAS Number: 31008-44-3
  • MF: C32H40N10O5
  • MW: 644.72
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-36

HDAC-IN-36 (compound 23 g) is an orally active and potent HDAC (histone deacetylase) inhibitor, with an IC50 of 11.68 nM (HDAC6). HDAC-IN-36 promotes apoptosis, autophagy and suppresses migration. HDAC-IN-36 shows anti-tumor and anti-metastatic activity, and can be used for breast cancer research[1].

  • CAS Number: 2482992-54-9
  • MF: C29H39N5O5
  • MW: 537.65
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YKL-5-124

YKL-5-124 is a novel potent, selective, and covalent CDK7 inhibitor (IC50=53.5 nM), inhibits CDK7/CycH/MAT1 enzymatic activity with IC50 of 9.7 nM; displays biochemical and cellular selectivity for CDK7 over structurally related kinases CDK12/13, and no significant activity against CDK2 and CDK9 (IC50>1 uM); targets and forms a covalent bond with CDK7- cysteine 312 (C312); inhibition of CDK7 by YKL-5-124 elicits a transcriptional signature distinct from that of THZ1, shows no discernible effect on RNA Pol II CTD phosphorylation; recapitulate THZ1-mediated effects on gene expression and CTD phosphorylation when combined with CDK12/13 inhibitor THZ531.

  • CAS Number: 1957203-01-8
  • MF: C28H33N7O3
  • MW: 515.618
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Hydroxymethyl-2’-O-(2-methoxyethyl)uridine

5-Hydroxymethyl-2’-O-(2-methoxyethyl)uridine is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 2095417-51-7
  • MF: C13H20N2O8
  • MW: 332.31
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Duocarmycin analog-2

Duocarmycin analog-2 is a potent DNA alkylating agent. Duocarmycin analog-2 can be used of synthetic immunoconjugate. Duocarmycin analog-2 has antitumor activity[1].

  • CAS Number: 1164275-01-7
  • MF: C29H23ClN4O3
  • MW: 510.97
  • Catalog: DNA Alkylator/Crosslinker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Miriplatin

Miriplatin is a chemotherapy agent which belongs to the class of alkylating agents.

  • CAS Number: 141977-79-9
  • MF: C34H68N2O4Pt
  • MW: 763.999
  • Catalog: DNA Alkylator/Crosslinker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Epitaxol

7-epi-Taxol is an active metabolite of taxol, with activity comparable to that of taxol against cell replication, promoting microtubule bundle formation and against microtubule depolymerization.

  • CAS Number: 105454-04-4
  • MF: C47H51NO14
  • MW: 853.906
  • Catalog: Microtubule/Tubulin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 957.1±65.0 °C at 760 mmHg
  • Melting Point: 168-170?C
  • Flash Point: 532.6±34.3 °C

iso-Chamaejasmin

Isochamaejasmin is a biflavonoid with anti-cancer, antiplasmodial and insecticidal activities. Isochamaejasmin displays a potent NF-κB (NF-κB) activation activity. Isochamaejasmin could cause DNA damage and induce Apoptosis via the mitochondrial pathway in AW1 cells[1][2]. Isochamaejasmin also has a moderate antiplasmodial activity (IC50 of 7.3 μM for P. falciparum) and relatively low cytotoxicity (CC50 of 29.0 μM)[3].

  • CAS Number: 93859-63-3
  • MF: C30H22O10
  • MW: 542.490
  • Catalog: Apoptosis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 932.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 314.2±27.8 °C

7’-OH-N-trityl morpholinothymine

7’-OH-N-trityl morpholinothymine (PMO Thymidine Precusor) is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 914361-76-5
  • MF: C29H29N3O4
  • MW: 483.56
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMV688845

MMV688845 is a nontuberculous mycobacteria (NTM) RNA polymerase inhibitor with bactericidal activity against Mycobacterium abscessus and anti-tuberculosis efficacy[1].

  • CAS Number: 2208962-35-8
  • MF: C24H25N3O3S
  • MW: 435.54
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-[(2,4-dichlorophenyl)methyl]-2-methyl-N-pentylsulfonylbenzimidazole-5-carboxamide

FK614 is an orally active, potent, selective PPARγ modulator (SPPARM). FK614 has different effects on the activation of PPARγ at each stage of adipocyte differentiation. FK614 is a nonthiazolidinedione insulin sensitizer. FK614 can be used for the research of hyperglycemia, hypertriglyceridemia, glucose intolerance and type 2 diabetes[1][2][3].

  • CAS Number: 193012-35-0
  • MF: C21H23Cl2N3O3S
  • MW: 468.39700
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MSC2504877

MSC2504877 (MSC-2504877) a novel small molecule selective tankyrase inhibitor with IC50 of 0.7/0.8 nM against TNKS1/2, shows 771-fold selectivity for TNKS1 over PARP1 (IC50=0.54 uM); increased AXIN2 protein levels and decreased β-catenin levels in APC mutant COLO320DM colorectal tumour cells, suppressed canonical Wnt signalling in SW480 cell line, inhibits the growth of APC mutant colorectal tumour cells; enhances G1 cell cycle arrest and cellular senescence in tumour cells when combined with CDK4/6 inhibitor Palbociclib, suppresses the upregulation of Cyclin D2 and Cyclin E2 caused by palbociclib and enhances the suppression of pRb; Palbociclib plus MSC2504877 combination suppresses hyperproliferation in Apc defective cells in vivo.

  • CAS Number: 1460286-21-8
  • MF: C17H18N2O2
  • MW: 282.343
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hesperadin

Hesperadin is an ATP-competitive inhibitor of aurora B kinase with an IC50 of 250 nM.

  • CAS Number: 422513-13-1
  • MF: C29H32N4O3S
  • MW: 516.654
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Longdaysin

Longdaysin is a CK1α, CK1δ, and extracellular signal-regulated kinase 2 (ERK2) inhibitor with IC50s of  5.6 µM, 8.8 µM, and 52 µM, respectively[1][2].

  • CAS Number: 1353867-91-0
  • MF: C16H16F3N5
  • MW: 335.33
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A